The stratum corneum is the superficial cornified layer of the skin that provides a barrier to water evaporation and, as such, is essential for terrestrial life. In addition to preventing water loss, the stratum corneum also reduces the permeation of undesirable molecules from the external environment. The stratum corneum consists of dead cells (corneocytes) embedded in a lipid-rich (fatty-acid, ceramide, cholesterol) matrix. Both the corneocytes and the intracelluar lipids are derived from epidermal keratinocytes. This structure of corneocytes embedded in lipids have given rise to a brick (corneocytes) and mortar (lipids) model of stratum corneum structure and function. It is thought that much of the barrier properties of the skin can be attributed to this structure. Substances deposited on the skin must traverse this structure through a tortuous path to gain access the underlying viable layers of the skin. Substances that are irritating to the skin often initiate an elaborate cascade of immunological events once they contact viable skin cells. These events ultimately lead to skin inflammation.
In particular, nasolabial skin is more vulnerable to skin irritation than many other sites on the body. This vulnerability is due to the decreased barrier function of nasolabial skin relative to other body sites. The rate of water loss through the skin can be measured and is indicative of the barrier properties of the skin12. A low level of water loss through the skin is normal. Movement of water through the skin is often referred to as Transepidermal Water Loss (TEWL) and is typically expressed as gxc2x7Mxe2x88x922xc2x7hrxe2x88x921. TEWL readings are routinely used to determine the barrier properties of a skin site at any given point in time13. Normally, significant differences in TEWL values can be found between disparate anatomical sites14. Studies have shown that the barrier properties of facial skin are significantly lower than other sites on the body. Indeed, differences in barrier properties between various sites on the face itself have been observed14,15. Indeed, the TEWL values obtained for nasolabial skin were among the highest values obtained on the face. With few exceptions, it appears that the face, and more specifically, nasolabial skin, has the lowest barrier properties of any skin site on the human body.
The barrier function of the skin with regard to moisture barrier, as measured by TEWL, often correlates with the skin""s ability to exclude exogenous substances as well14,16. As the barrier to water decreases (increasing TEWL value) exogenously applied molecules are often more likely to penetrate to the viable layers of the skin12. This suggests that nasolabial skin may be more permeable to topically applied irritants and therefore more susceptible to inflammation relative to other skin sites.
Skin barrier function can be compromised by a variety of insults. Examples of treatments known to diminish skin barrier function include, but are not limited to, physical treatments (abrasion, tape stripping, ultrasonics, electrical fields), enzymes, solvents, surfactants, and elevated ambient humidity 17,18,19,20,21,22,23. Repeated wiping of nasolabial skin with facial tissue can diminish skin barrier function due to abrasion. Insults that diminish skin barrier function can predispose skin to inflammatory events by the enhanced uptake of irritants through the stratum corneum.
Bodily fluids may contain skin irritants. For example, the nasal secretions of individuals experiencing colds or allergies contain a myriad of substances that can potentially irritate nasolabial skin. These substances include, but are not limited to, an array of biologically active components including cytokines, eicosanoids, enzymes, and various toxins. For example, the cytokines interleukin-1xcex2 (IL-1xcex2) and interleukin-8 (IL-8) are present in high concentrations in nasal secretions1,2,3. Likewise, the eicosanoids leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are also present at high concentrations in nasal secretions4,5,6,7,8. Additionally, the enzymes kinase, tryptase, phospholipase, and glycosydase are present in nasal secretions. Finally, nasal secretions can contain superantigens produced by the bacterium Staphylococcus aureus including staphylococcal enterotoxins A (SEA), B (SEB), and Toxic Shock Syndrome Toxin-1 (TSST-1) as well as other bacterial by-products. Furthermore, the cutaneous responses to topically applied cytokines, eicosanoids, enzymes, and superantigens have also been described9,10,11. 
Enzymes commonly found in other biological fluids, particularly proteases and lipases in feces, are known to damage skin barrier function and cause skin inflammation. For example, prolonged exposure of the skin to fecal proteases and lipases is thought to be a major cause of skin damage that leads to diaper dermatitis in infants. The care of skin in individuals with ostomies is difficult due to the frequent contact of digestive enzymes with skin surrounding the ostomy. These enzymes can degrade skin proteins and lipids and cause irritation of the skin. Bodily fluid enzymes can also cause or exacerbate psoriasis.
Therefore, bodily secretions contain a variety of irritants that can initiate skin inflammation. In addition, physical contact with other animals and plants can confer skin irritants to an individual, such as from poison ivy. Furthermore, other caustic inanimate materials, such as acidic chemicals, can cause skin irritation.
What is needed in the art today are novel mechanisms for preventing or mitigating skin inflammation due to the exceedingly complex mixture of irritants in bodily secretions and the environment.
A number of approaches are known for protecting the skin against the action of skin irritants. Examples include protective apparel, skin protectant formulations, and anti-inflammatory compositions.
Barrier compositions can provide demonstrable clinical benefits. However, it is known that while many compositions can retard the penetration of one type of irritant it may not afford a similar level of protection against others24,25. This evidence suggests that many currently available skin protectant formulations are unable to exclude a wide range of irritants that differ based on hydrophobicity, size, and/or chemical composition. Consequently, many skin protectant formulations may not provide adequate protection against a complex mixture of skin irritants.
Another method of addressing skin irritation due to contact with skin irritants is the use of anti-inflammatory compounds. The topical use of anti-inflammatory compounds does not protect the skin from coming in contact with an irritant. Instead, for many skin irritants, damage to the skin still occurs but the inflammatory response is mitigated by the anti-inflammatory substance. Therefore, the effect of anti-inflammatory compounds is exerted by influencing the biology of viable skin cells rather than by preventing the skin damage that elicits the inflammatory event in the first place.
PCT publication WO 97/38735 teaches the use of a singular sequestrant (organophilic clays; i.e. clays modified with hydrophobic substances), such as quarternium-18 bentonite, to absorb and deactivate fecal proteolytic enzymes to prevent diaper rash of the skin. A diaper fabric incorporating the organophilic clay dispersed in a super absorbent polymer is suggested, as well as other pharmaceutically suitable vehicles for the organophilic clay, such as lotions, emulsions, creams, gels, and aqueous vehicles. The reference teaches that compounds having C-8 and longer hydrocarbon chains should be excluded from the composition. The protective composition is specifically intended to act as a barrier to prevent fecal enzymes from contacting the skin. Further, lotions and aerosols containing organophilic clay, ion exchanged with a quaternary ammonium compound, are used to block and absorb plant allergens in U.S. Pat. Nos. 5,017,361 and 5,702,709. Additionally, art exists to describe the inclusion of non-modified clays into tissue products for purposes unrelated to skin health (U.S. Pat. Nos. 5,611,890 and 5,830,317).
Skin protectants that augment skin barrier properties to thwart the penetration of exogenous irritants can have skin health benefits. Various technological approaches to deliver these benefits are known to those skilled in the art. It is the object of this invention to provide novel compositions and methods necessary to protect skin from the irritants present in bodily secretions and the environment.
What is needed in the art are novel mechanisms to promote general skin health.
What is needed in the art are novel mechanisms to promote nasolabial skin health.
What is needed in the art are novel mechanisms to mitigate or prevent nasolabial skin irritation and inflammation due to the topical deposition of skin irritants present in nasal secretions. Novel approaches are needed as many of the skin irritants present in nasal secretions are unique to this biological fluid.
Thus, the present invention provides that skin inflammation can be caused by the penetration of inflammatory agents present in bodily secretions and the environment through the stratum corneum and into the underlying viable layers of the skin. For example, biologically active cytokines, eicosanoids, enzymes, and superantigens can permeate through the stratum corneum to the viable layers of the skin and elicit undesirable biological effects including skin inflammation. Therefore, the invention described herein provides for novel compositions and methods to help prevent undesirable skin symptoms caused by the deposition of nasal secretions on skin.
The present invention provides methods to prevent the penetration of skin irritants through the stratum corneum into the viable layers of the skin. In particular, the present invention provides methods of protecting against nasal secretion mediated skin inflammation. Thus, the present invention provides methods of promoting improved skin health.
One embodiment of the present invention is directed to a method of sequestering skin irritants with a skin irritant sequestering composition comprising a substrate containing a sequestering agent(s) with an affinity for skin irritants. One embodiment of the invention provides for a substrate containing a hydrophobic sequestering agent(s) for hydrophobic skin irritants. Another embodiment of the invention provides for a substrate containing a hydrophilic sequestering agent(s) for hydrophilic skin irritants. In an alternate embodiment, the invention is directed toward a method of using a skin irritant sequestering composition comprising a substrate containing thereon a sequestering agent(s) with an affinity for hydrophobic skin irritants present in nasal secretions and (a) sequestering agent(s) with an affinity for hydrophilic irritants present in nasal secretions.
In another embodiment, the hydrophilic and hydrophobic skin irritant sequestering agents are isolated from each other in discrete regions of the substrate.
In a further embodiment, the discrete regions of the substrate are defined by a pattern configuration wherein the hydrophilic and hydrophobic sequestering agents are each relegated to separate regions of the pattern on the substrate.
In a further embodiment, the substrate is multi-layered and the discrete regions of the substrate are defined by the hydrophilic and hydrophobic sequestering agents each being present on separate plies and/or layers of a given ply of the substrate.
In a further embodiment, the substrate is composed of multiple distinct fibers and the discrete regions of the substrate can be defined by the hydrophilic and hydrophobic sequestering agents each being present on separate fibers of the substrate. These fibers may be coated or filled with the sequestering agent material. The aforementioned fibers may comprise all or a fraction of the total fibers used to make the substrate.
The substrate used in the present invention can be prepared from a variety of materials. Suitable materials comprise any matter that does not hinder the sequestering agents"" affinity for binding skin irritants. One example of a suitable substrate is a tissue prepared from plant fibers. Other examples include, but are not limited to, woven and nonwoven webs, spunbonded fabric, meltdown fabric, knit fabric, wet-laid fabric, scrims, synthetic fibers, natural fibers and combinations thereof. It is to be understood that these suitable substrates are not mutually exclusive and can be used in combination.
In one embodiment, to be effective, sequestering agents must bind skin irritants either covalently or non-covalently. Examples of skin irritants present in nasal secretions include, but are not limited to, cytokines (such as interleukin-1xcex1, IL-xcex2, and IL-8), eicosanoids (such as PGE2 and LTB4), and superantigens (such as those produced by the bacterium Staphylococcus aureus including staphylococcal enterotoxins A, B, and Toxic shock syndrome toxin-1). Skin irritants are also present in feces, such as trypsin and elastase. The examples of skin irritants listed above are not intended to represent an exhaustive list, rather, they are incorporated to aid in illustrating the utility of the invention. Certain embodiments of the present invention include using substrates comprising both hydrophilic and hydrophobic sequestering agents having an affinity for binding the irritants listed above.
The sequestering agents could be any material(s) capable of binding skin irritants present in bodily fluids such as nasal secretions. Examples of suitable sequestering agents include, but are not limited to, modified and non-modified clay, modified and non-modified silica, modified and non-modified titanium dioxide, and modified and non-modified refractory metal oxides. The invention provides that hydrophilic skin irritants, such as cytokines, bind to hydrophilic sequestering agents, such as non-modified clay for example. Likewise, the invention provides that those hydrophobic skin irritants, such as eicosanoids, bind to hydrophobic sequestering agents, such as modified clay for example.
The present invention provides methods of sequestering inflammatory irritants on the outermost layers of the stratum corneum. Deposition of sequestrants on the outer layer of the skin will prevent skin irritants from penetrating into the underlying viable layers of the skin, thus providing a skin health benefit. In one embodiment, this is accomplished by administering to the individual""s skin an effective amount of sequestering agent(s) capable of binding skin irritants present in nasal secretions.
Sequestering agents can be imparted to the skin""s surface via a substrate and then removed by normal desquamatory events (normal sloughing of the outermost layer of the skin) and/or personal hygiene. The transfer of sequestering agents from the substrate to the skin can be accomplished via any number of suitable vehicles including, but not limited to, anhydrous formulations, gels, pastes, creams, powders, lotions, emulsions, or aqueous formulations or any combination thereof.
Alternatively, sequestering agents may remain bound to a skin irritant composition to minimize their interaction with the skin. In this case, the irritants are removed from the skin by binding to one or more sequestrants present on a substrate. It is understood that these two distinct modes of action (binding irritants to sequestrants deposited on the skin""s surface or binding irritants to sequestrants present on a substrate and therefore removing the irritants from the skin""s surface to a substrate) are not mutually exclusive and can be combined.